Urea kinetics and dialysis treatment time predict vancomycin elimination during high-flux hemodialysis.
BACKGROUND
Hemodialysis sessions with high-flux filters ask for a reconsideration of the kinetics of xenobiotics. The aim of this study was to analyze whether individual high-flux hemodialysis treatment parameters are of predictive value for dosing guidelines, with use of vancomycin as a model compound.


METHODS
Twenty-six patients receiving high-flux hemodialysis were studied prospectively. After an intravenous infusion of 1000 mg or 500 mg vancomycin, respectively, six to eight blood samples were collected within a period of 5 to 9 days, including one hemodialysis session. Serum vancomycin concentrations were measured by HPLC. Nonlinear mixed-effects modeling (NONMEM) was used to fit a two-compartment population pharmacokinetic model to the data of 20 patients; the data of the remaining six patients (group II) were used for a prospective evaluation of the model.


RESULTS
A linear relationship was found between vancomycin filter clearance (CLDV) and urea filter clearance (CLDBUN), derived from Kt/V (the product of urea clearance [K] and dialysis treatment time [t], standardized for the urea volume of distribution [V]). Mean (coefficient of variation) steady-state volume of distribution was 1.05 L/kg (22%), CLDV was 0.336.CLDBUN (13%), and residual interdialytic clearance was 2.25 ml/min (90%) in patients with creatinine clearance values (CLCR) below 2 ml/min and 2.25 ml/min + 0.59.CLCR (32%) in patients with CLCR values above 2 ml/min. The model predicted predialysis vancomycin concentrations before the first and the second postinfusion dialysis session in the six patients of group II, with a deviation of 1.8 +/- 1.0 mg/L and 0.8 +/- 0.5 mg/L, respectively.


CONCLUSIONS
The described population pharmacokinetic model allows individualization of vancomycin dosing intervals in patients receiving hemodialysis, based on patient characteristics and urea kinetic modeling.
Schaedeli
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Department of Medicine, University of Berne, Bern, Switzerland.
Uehlinger
D E
DE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D006435:Renal Dialysis / Q000379:methods; D013997:Time Factors; D014508:Urea / Q000097:blood*; D014640:Vancomycin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D014640:Vancomycin; D014508:Urea